What is the initial treatment for a patient with suspected adrenal insufficiency?

Initial Treatment for Suspected Adrenal Insufficiency

If adrenal crisis is suspected based on clinical presentation (unexplained collapse, hypotension, vomiting, or profound weakness), immediately administer IV hydrocortisone 100 mg bolus followed by 100 mg every 6-8 hours, plus 0.9% saline infusion at 1 L/hour—never delay treatment for diagnostic testing. 1, 2

Immediate Assessment and Emergency Management

The critical decision point is determining whether the patient is clinically unstable or stable:

For Unstable Patients (Suspected Adrenal Crisis)

• Administer IV hydrocortisone 100 mg immediately as a bolus, then continue with 100 mg every 6-8 hours until clinical recovery 1, 2, 3
• Infuse 0.9% saline at 1 L/hour (minimum 2L total) to correct hypotension and volume depletion 1, 2
• Draw blood for cortisol and ACTH measurement before giving hydrocortisone if possible, but do not delay treatment to obtain these samples 4, 1
• Identify and treat the precipitating cause (infection, trauma, surgery) 2

Critical pitfall to avoid: The American College of Internal Medicine emphasizes that delaying treatment while waiting for diagnostic test results in suspected adrenal crisis can be fatal 1, 2. Mortality is high if untreated 4.

Alternative Emergency Approach When Diagnosis Uncertain

• If you need to treat emergently but want to preserve the ability to perform diagnostic testing later, use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone does not interfere with cortisol assays 4, 1, 5
• However, dexamethasone lacks mineralocorticoid activity and is inadequate for primary adrenal insufficiency, so this should only be a temporary measure 4

For Stable Patients (Suspected but Not Critical)

Initial Diagnostic Workup

• Obtain paired morning (8 AM) serum cortisol and plasma ACTH as first-line tests 4, 1, 2, 3
• Order basic metabolic panel to assess for hyponatremia (present in 90% of cases) and hyperkalemia (present in only ~50% of cases) 4, 1, 2
• Measure DHEAS levels to help distinguish primary from secondary adrenal insufficiency 3

Interpretation of Initial Results

Primary adrenal insufficiency is diagnosed when:

• Morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in acute illness 4, 2, 3
• This pattern is often accompanied by hyponatremia and sometimes hyperkalemia 4, 2

Secondary adrenal insufficiency is suggested when:

• Morning cortisol 140-275 nmol/L (5-10 μg/dL) with low or inappropriately normal ACTH 4, 3

If cortisol levels are intermediate (140-400 nmol/L or 5-14.5 μg/dL):

• Perform cosyntropin stimulation test to definitively confirm or exclude the diagnosis 4, 1, 3
• Administer 0.25 mg (250 mcg) cosyntropin IV or IM 4, 1
• Measure serum cortisol at baseline, 30 minutes, and 60 minutes post-administration 4, 1
• Peak cortisol <500 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency 4, 1, 3
• Peak cortisol >550 nmol/L (>18-20 μg/dL) excludes adrenal insufficiency 4, 1

Treatment Based on Severity for Stable Patients

Mild to Moderate Symptoms (Outpatient Management)

• Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg at 7 AM, 5 mg at noon, 2.5-5 mg at 4 PM) 4, 3, 6
• Alternative: Prednisone 3-5 mg daily 4, 7, 3
• For moderately symptomatic patients, initiate at 2-3 times maintenance dose initially 4

Primary vs. Secondary Adrenal Insufficiency

For primary adrenal insufficiency specifically:

• Add fludrocortisone 0.05-0.1 mg daily for mineralocorticoid replacement 4, 8, 3
• Typical range is 50-200 µg daily, adjusted based on blood pressure, salt cravings, and plasma renin activity 4, 8
• Encourage unrestricted sodium salt intake 4

For secondary adrenal insufficiency:

• Glucocorticoid replacement alone is sufficient (no mineralocorticoid needed) 4
• Important warning: If concurrent hypothyroidism exists, start corticosteroids several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis 4, 9

High-Risk Clinical Scenarios Requiring Immediate Treatment

• Any patient taking ≥20 mg/day prednisone (or equivalent) for ≥3 weeks who develops unexplained hypotension should be presumed to have adrenal insufficiency 4, 1
• Hypotension requiring high-dose or multiple vasopressors that remains refractory to treatment 4
• Unexplained collapse with gastrointestinal symptoms (vomiting, diarrhea) 4, 2

Essential Patient Education and Follow-Up

• All patients require education on stress dosing: double or triple dose during illness, fever, or physical stress 4, 6
• Prescribe emergency injectable hydrocortisone 100 mg IM kit with self-injection training 4, 3, 6
• Patients must wear medical alert bracelet or necklace indicating adrenal insufficiency 4, 1, 3
• Annual screening for associated autoimmune conditions (thyroid function, diabetes, vitamin B12, celiac disease) in primary adrenal insufficiency 1

Common Pitfalls to Avoid

• Never rely on electrolyte abnormalities alone to make or exclude the diagnosis—hyperkalemia occurs in only ~50% of cases, and some patients have normal electrolytes 4, 1
• Do not attempt cortisol testing in patients actively taking corticosteroids—the assay measures both endogenous and exogenous steroids, yielding uninterpretable results 4
• Avoid abrupt discontinuation of glucocorticoid replacement therapy in confirmed cases—this is lifelong treatment for non-iatrogenic causes 4
• Do not use dexamethasone for chronic replacement therapy in primary adrenal insufficiency due to lack of mineralocorticoid activity 4